Atypical Rett syndrome diagnosis by molecular testing

Abstract Rett syndrome is a neurodevelopmental disorder that leads to regression in language and motor skills. In most cases, it is caused by genetic mutations in the methyl-CpG-binding protein 2 gene ( MECP2 ). Rett Syndrome occurs almost exclusively in girls and may be easily misdiagnosed, because its spectrum of clinical characteristics is overlapping with characteristics of other disorders such as autism, ataxic cerebral palsy, atypical Angelman's syndrome, spinocerebellar degeneration, etc. A 16-year-old girl with behavior within the autistic spectrum disorder, moderate to severe intellectual delay and subtle dysmorphic features enrolled in the Shafallah Center for children with special needs, School Unit 1. She is shy, with no sustained eye contact and has secondary seizures. She can use her hands in eating, drinking, painting in the class and she can hold a pencil between the index finger and thumb to do lines and circles, her history shows no regression. The clinical characteristics are closer to the autistic spectrum disorders than to the Rett syndrome. In order to avoid misdiagnosis between Autism and Rett syndrome, a genetic testing of the MECP2 was realized in the Shafallah Medical Genetics Center, by sequencing and Multilocus Ligation Probe Amplification (MLPA). The sequencing analysis showed no variations in both directions, while the MLPA analysis detected a deletion of 0.6-2 kb in exon 4 of MECP2 . The tests were repeated twice and the result was confirmed. The molecular testing result supports a Rett syndrome diagnosis, while the clinical characteristics of the patient are not the typical Rett syndrome features. The case demonstrates that the spectrum of the clinical characteristics of the Rett syndrome is broader than is generally considered. This fact makes the diagnosis of Rett syndrome difficult by relying only in the clinical manifestations. Cases like this enforce the role of the molecular testing as a strong diagnostic tool.